Purinergic Ca2+ signaling in myenteric neurons via P2 purinoceptors

Christofi, Fievos L.; Guan, Zhen; Wood, Jackie D.; Baidan, L.V.; Stokes, Bradford T.

doi:10.1152/ajpgi.1997.272.3.g463

Cited by 23 publications

(26 citation statements)

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“…Here they appear to mediate a hyperpolarization of the membrane due to an opening of the calcium-activated potassium conductance [85,101]. This has been supported by calcium imaging studies that suggest a P2Y receptor is coupled to release of internal calcium [35] possibly through a P2Y 1 receptor [20].…”

Section: Slow Synaptic Transmissionmentioning

confidence: 80%

“…Adenosine may then act at its own receptors before itself being broken down to inosine by the enzyme adenosine deaminase. Studies in the ENS have failed to show an appreciable effect when ATP is applied and P1 receptors are blocked [35,36] or when breakdown of ATP is prevented [37], suggesting that this route for adenosine formation, although plausible, may not be physiologically relevant.…”

Section: Adenosine and P1 Receptors In The Ensmentioning

confidence: 99%

“…Christofi et al [35] looked at cultured myenteric neurons from guinea pig and showed that there is a rise in intracellular calcium associated with application of ATP and activation of P2 receptors. This was confirmed in submucosal neurons where a fast P2X receptor-mediated and a slow P2Y receptor-mediated calcium rise and depolarization were identified [100].…”

Section: Properties Of P2y Receptors In the Ensmentioning

confidence: 99%

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Purinergic receptors and synaptic transmission in enteric neurons

Ren

Bertrand

2007

Purinergic Signalling

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Purines such as ATP and adenosine participate in synaptic transmission in the enteric nervous system as neurotransmitters or neuromodulators. Purinergic receptors are localized on the cell bodies or nerve terminals of different functional classes of enteric neurons and, with other receptors, form unique receptor complements. Activation of purinergic receptors can regulate neuronal activity by depolarization, by regulating intracellular calcium, or by modulating second messenger pathways. Purinergic signaling between enteric neurons plays an important role in regulating specific enteric reflexes and overall gastrointestinal function. In the present article, we review evidence for purine receptors in the enteric nervous system, including P1 (adenosine) receptors and P2 (ATP) receptors. We will explore the role they play in mediating fast and slow synaptic transmission and in presynaptic inhibition of transmission. Finally, we will examine the molecular properties of the native receptors, their signaling mechanisms, and their role in gastrointestinal pathology. Keywords

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Section: Slow Synaptic Transmissionmentioning

confidence: 80%

Section: Adenosine and P1 Receptors In The Ensmentioning

confidence: 99%

Section: Properties Of P2y Receptors In the Ensmentioning

confidence: 99%

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Purinergic receptors and synaptic transmission in enteric neurons

Ren

Bertrand

2007

Purinergic Signalling

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“…Nicotinic and P2X channels of neurons are permeable to Na¤ and Ca¥, suggesting that their intracellular accumulation could mediate the inhibitory interaction between these channels. This hypothesis is supported by the fact that nicotinic and P2X receptors of enteric neurons are known to be permeable to these cations (Trouslard et al 1993;Barajas-L opez et al 1994Barajas-L opez et al , 1996aChristofi et al 1997). However, we have ruled out such a possibility, by showing that the interaction is not affected by the absence of Ca¥ or Na¤ in the intracellular and extracellular solutions.…”

Section: Discussionmentioning

confidence: 92%

Functional interactions between nicotinic and P2X channels in short‐term cultures of guinea‐pig submucosal neurons

Barajas‐López

Espinosa-Luna

Zhu

1998

The Journal of Physiology

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How these subunits organize themselves to form ion channels in native membrane is not completely understood (see Bean, 1992). Recently, Nakazawa (1994a) suggested that there is an overlap of P2X and nicotinic channels, and that ATP could open a subpopulation of nicotinic channels by binding to P2X receptors in rat sympathetic neurons. This 'channel overlap' hypothesis was based on the findings that channel activation by ATP and ACh is not independent. Indeed, the cationic current activated by ACh (IACh; which was selectively blocked by hexamethonium) occluded the smaller cationic current induced by ATP (IATP; which was selectively blocked by suramin), in rat sympathetic neurons. Similar observations have been reported in rat phaeochromocytoma PC12 cells by Nakazawa et al. (1991). In the present study our aim was to functionally characterize a putative inhibitory interaction between P2XJournal of Physiology (1998), 513.3, pp. 671-683 671 Functional interactions between nicotinic and P2X channels in short-term cultures of guinea-pig submucosal neurons 1. Functional interactions between nicotinic and P2X receptors in submucosal neurons were investigated. Whole-cell currents induced by ACh (IACh) and ATP (IATP) were blocked by hexamethonium and pyridoxalphosphate-6-azophenyl-2',4'-disulfonic acid (PPADS), respectively. Currents induced by simultaneous application of the two transmitters (IACh+ATP) were only as large as the current induced by the most effective of these substances. This current occlusion indicates that activation of nicotinic and P2X channels is not independent. 2. Kinetic parameters of IACh+ATP indicate that they are carried through channels activated by either substance. In agreement with this interpretation, both IACh and IATP amplitudes were decreased when ATP and ACh were applied simultaneously, whereas no cross-desensitization was observed when nicotinic and P2X receptors were desensitized individually. 3. Current occlusion was observed at membrane potentials of −60 and +10 mV, when IACh and IATP were inward. However, when these currents were outward (at +40 mV), current occlusion was not observed. Current occlusion was still observed at +40 mV in experiments in which the reversal potential of these currents had been adjusted to more positive values. 4. Current occlusion occurred as soon as currents were detected (< 5 ms), was still present in the absence of Ca¥, Na¤ or Mg¥, and after adding staurosporine, genistein, K-252a, or N_ethylmaleimide to the pipette solution. Similar observations were noted after substituting á,â-methylene ATP for ATP, or GTP for GTP-ã-S in the pipette and in experiments carried out at 36, 23 and 9°C. 5. We propose that nicotinic and P2X channels are in functional clusters of at least two, and that the influx of ions through one activates (through allosteric interactions) a mechanism that inhibits the other channel.8157

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“…ATP and 5-HT are known to modulate the potassium membrane conductance of enteric neurons via G proteinlinked receptors (4,12,19). To isolate the ionic membrane currents mediated by activation of ligand-gated channels, the experiments were carried out in the presence of Cs ϩ (a potassium channel blocker) and currents were measured by the whole cell patch-clamp configuration.…”

Section: Methodsmentioning

confidence: 99%

Inhibitory interactions between 5-HT₃ and P2X channels in submucosal neurons

Barajas‐López

Montaño

Espinosa-Luna

2002

American Journal of Physiology-Gastrointestinal and Liver Physi

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Barajas-Ló pez, Carlos, Luis M. Montañ o, and Rosa Espinosa-Luna. Inhibitory interactions between 5-HT3 and P2X channels in submucosal neurons. Am J Physiol Gastrointest Liver Physiol 283: G1238-G1248, 2002. First published June 5, 2002 10.1152/ajpgi.00054.2002-Inhibitory interactions between 5-HT subtype 3 (5-HT3) and P2X receptors were characterized using whole cell recording techniques. Currents induced by 5-HT (I5-HT) and ATP (IATP) were blocked by tropisetron (or ondansetron) and pyridoxalphosphate-6-azophenyl-2Ј,4Ј-disulfonic acid, respectively. Currents induced by 5-HT ϩ ATP (I5-HTϩATP) were only as large as the current induced by the most effective transmitter, revealing current occlusion. Occlusion was observed at membrane potentials of Ϫ60 and 0 mV (for inward currents), but it was not present at ϩ40 mV (for outward currents). Kinetic and pharmacological properties of I5-HTϩATP indicate that they are carried through 5-HT3 and P2X channels. Current occlusion occurred as fast as activation of I5-HT and IATP, was still present in the absence of Ca 2ϩ or Mg 2ϩ , after adding staurosporine, genistein, K-252a, or N-ethylmaleimide to the pipette solution, after substituting ATP with ϰ,␤-methylene ATP or GTP with GTP-␥-S in the pipette, and was observed at 35°C, 23°C, and 8°C. These results are in agreement with a model that considers that 5-HT3 and P2X channels are in functional clusters and that these channels might directly inhibit each other. autonomic neurons; enteric neurons; ligand-gated channels; ion channels; ATP; ATP receptors; P2X receptors; serotonin; 5-hydroxytryptamine; 5-hydroxytryptamine 3 channels; 5-hydroxytryptamine 3 receptors; fast neurotransmission 5-HT AND ATP are known to play a role as neurotransmitters (17,35,37,38) by directly activating cationic channels in the postsynaptic membrane, which are named 5-HT 3 and P2X receptors, respectively. 5-HT 3 receptors are part of the nicotinic ligand-gated channel superfamily, and two different subunits have been cloned. Each of these subunits have four transmembrane domains (14,29). Of the seven different P2X subunits that have been cloned, each subunit appears to cross the membrane only twice (10,16,24). Some of these subunits are able to form homomeric functional cation channels, e.g., P2X 2 and 5-HT 3A . Other ones appear to participate only in heteromeric channels, e.g., P2X 6 and 5-HT 3B (14,27). Current models of 5-HT 3 and P2X channels propose that these channels are formed by a combination of five and three subunits, respectively (14, 32). Recent experimental evidence indicates that the nicotinic acetylcholine (nACh) channels and P2X are not independent and that they can inhibit each other when they are simultaneously activated (6,39). This inhibitory interaction is very fast and might be mediated by an allosteric interaction between nACh and P2X channels. A similar crossinhibition between the P2X 2 and nicotinic ϰ3␤ 4 -receptor subtypes was observed when these were coexpressed in Xenopus oocytes (25). Similar interactions have been sh...

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Purinergic Ca2+ signaling in myenteric neurons via P2 purinoceptors

Cited by 23 publications

References 0 publications

Purinergic receptors and synaptic transmission in enteric neurons

Purinergic receptors and synaptic transmission in enteric neurons

Functional interactions between nicotinic and P2X channels in short‐term cultures of guinea‐pig submucosal neurons

Inhibitory interactions between 5-HT₃ and P2X channels in submucosal neurons

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